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Jobu Sugita, Akira Matsuda, Yosuke Asada, Nobuyuki Ebihara, Akira Murakami, Susumu Nakae; The Role of Th2 cytokines in Mouse Models of Papain-Induced Conjunctivitis.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):304.
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© ARVO (1962-2015); The Authors (2016-present)
In ARVO 2015, we reported significant reduction of eosinophil infiltration in papain-soaked soft contact lens (papain-CL) induced mouse allergic conjunctivitis using interleukin-33 (IL-33) knockout mouse. Since papain-CL conjunctivitis model also accompanied increase of Th2 cytokine expression, we further investigated involvements of Th2 cytokines in papain-CL conjunctivitis using IL-13 deficient (IL-13/Tomato knock-in), IL-4 deficient (IL-4/G4 knock-in), and IL−5 knockout mice.
Papain-CL was installed into the conjunctival sac of C57BL6-IL-13/Tomato, IL-4/G4, IL-13/TOMATO, IL-5 KO, IL-33 KO and C57BL6 wild-type mice and the eyes were sampled at day 5. The eosinophil infiltration of papain-SCL conjunctivitis was evaluated histologically and cytokine expression was examined by real-time PCR. Immunoshistochemical staining using mouse basophil marker MCPT8 were also carried out.
Significant attenuation of the numbers of infiltrating eosinophils was observed in the papain-SCL conjunctivitis models using IL-4/G4 knock-in mice compared to wild-type mice, but there was no significant difference among IL-5KO, IL13/TOMATO and wild-type mice. Il4, il5, il13, ccl5, and ccl1 mRNA expression was significantly lower in the conjunctivae of the papain-SCL conjunctivitis models using IL-4 deficient (IL-4/G4 knock-in) mice compared to wild-type mice. MCPT8 immunoshistochemical staining showed significant reduction of the basophil numbers in the papain-CL conjunctivitis models using IL-33KO (6 ± 0.9 basophils per one slides) mice compared to those of the wild type mice (17± 0.9 basophils per one slides).
Among the Th2 cytokines, IL-4 may have dominant roles for pathophysiology of papain-CL conjunctivitis. Since basophils are known as an abundant source of IL-4, significant reduction of basophils in the IL-33 KO mouse is consistent with our previous results showing the attenuated eosinophilic inflammation in IL-33KO mice in papain-CL conjunctivitis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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